Chromatographic separation

ABSTRACT

The invention relates to an equipment for fractionating a solution by a sequential SMB process, which equipment comprises a feed column and one or several other columns, which include a chromatographic separation resin bed. The equipment of the invention is characterized in that the feed column consists of or comprises a compartment where the resin bed is shallower than that of one or more of the other columns of the equipment. The invention also relates to a method for fractionating a solution into two or more fractions with the equipment of the invention.

FIELD OF THE INVENTION

The present invention relates to chromatographic simulated moving bedequipments and methods for fractionating solutions using chromatographicsimulated moving bed processes. More specifically, the present inventionrelates to a sequential chromatographic simulated moving bed equipmentand a method for fractionating solutions using a shallow resin bedcompartment as a feed column. The equipment and the method of theinvention can be applied to the fractionation of solutions like molassesolutions, vinasse solutions and sulphite cooking liquors, for example.

BACKGROUND OF THE INVENTION

Continuously operated chromatographic separation processes commonlyemploy a simulated moving bed method (SMB method), which is used in avariety of different applications. The SMB method may be continuous orsequential or comprise a combination of a continuous method and asequential method. In the continuous SMB process, all fluid streamstypically flow continuously. In the sequential SMB process, some of thefluid streams do not flow continuously. The sequential SMB processcommonly comprises three basic phases: a feeding phase, an elution phaseand a circulation phase. During the feeding phase, a feed solution andpossibly also an eluant during a simultaneous eluting phase, isintroduced into a predetermined column containing one or more partialpacked beds, and simultaneously a product fraction or fractions arewithdrawn. During the eluting phase, the eluant is introduced into apredetermined partial packed bed or predetermined partial packed beds,and during these phases two, three or even four product fractions arewithdrawn. During the circulation phase all columns are connected into aloop, whereby no feed solution or eluant is supplied to the partialpacked beds and no product fractions are withdrawn. However, circulationas such takes place during all three phases.

The continuous SMB process has been described, for example, in U.S. Pat.No. 2,985,589 (Universal Oil Prod. Co). In this process the mixture tobe fractionated is introduced into one partial packed bed and an eluantis introduced into another partial packed bed, and two product fractionsare withdrawn substantially simultaneously. U.S. Pat. No. 5,198,120(Organo KK) describes a continuous SMB process in which the feed pointis fixed. The feed is introduced sequentially once a cycle andsimultaneously with the introduction of the feed a first extractfraction and raffinate are taken out from the system. The examples ofthis patent use a simulated moving bed consisting of eight packedcolumns linked with each other in series, and each column, including thefeed column, having an equal packed bed height.

Sequential SMB processes are described in U.S. Pat. No. 4,332,623(Mitsubishi Chem. Ind.), U.S. Pat. No. 4,379,751 (Sanmatsu Kogyo) andU.S. Pat. No. 4,970,002 (Mitsubishi Kasei Tech. Eng.), for instance.FIG. 1 of the above-mentioned U.S. Pat. No. 4,332,623 (Mitsubishi Chem.Ind.) discloses an apparatus for carrying out said method, whichapparatus has three unit packed beds, which may be of the same ordifferent size. Furthermore, the above-mentioned U.S. Pat. No. 4,970,002(Mitsubishi Kasei Tech. Ing.) discloses a chromatographic separationapparatus including two packed beds, which may be the same or differentin terms of bed capacity or the volume of the packing material.

A sequential SMB process for the recovery of betaine and sucrose frombeet molasses is described in U.S. Pat. No. 5,127,957 (Heikkilä, H. etal.). To increase the separation capacity, yields and fraction puritiesand fraction dry substance concentrations, SMB modes including two ormore loops or two or more separation profiles have been developed. InU.S. Pat. No. 6,093,326 (Danisco Finland Oy) and U.S. Pat. No. 5,637,225(Xyrofin Oy) SMB processes including multiple loops are described. U.S.Pat. No. 6,224,776 (Cultor Corp.) discloses a method for fractionating asolution into two or more fractions in a SMB process where theseparation system comprises at least two separation profiles in the sameloop.

WO 01/54790 (Amalgamated Res. Inc.) describes a column apparatus for afluid processing system containing a shallow bed of material betweenfluid transporting fractals of large active surface area. In saidapparatus, said shallow bed of material has been provided as a columnhaving greater diameter than height.

However, it does not appear from any of the above-mentioned referencesthat the design of the feed column would differ significantly from thatof the other columns used in the process.

One problem associated with the above SMB process modes is the so-calledviscous fingering phenomenon which in turn causes the tailing effect ofthe chromatograms. Another problem with these SMB processes is therandom resin movement which, as being irregular and turbulent, blendsthe frontiers and decreases the separation capacity.

It has now been found in accordance with the present invention that byusing a shallow resin bed compartment as the feed column the problemsabove can be overcome or alleviated. With the use of a shallow resin bedcompartment as the feed column, the viscous fingering and the randomresin movement can be reduced. This leads to an improved separationprofile in the feed column, which permits improved performance of thelater columns.

DEFINITIONS RELATING TO THE INVENTION

In the present invention, a column refers to a section of thechromatographic equipment which holds a chromatographic separation resinbed and which comprises a forepart for feeding eluant and/or feedsolution and a rear part for withdrawing product fractions. A feedcolumn refers to a section of the chromatographic equipment which holdsa chromatographic separation resin bed and which comprises a forepartfor feeding a feed solution and a rear part for withdrawing productfractions. A column may be composed of one or several compartments. Acompartment refers to a section of a column (which contains a part forfeeding eluant and/or feed solution, or a part for withdrawing productfractions or both).

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows how sucrose is divided into the residual, sucrose andbetaine fractions (RF, SF and BF fractions) in the fractionation of amolasse solution using different feed column lengths, i.e. where thefirst column is 1.45 m, 3.00 m or 1.95 m, respectively.

FIG. 2 a shows the on-line concentration and conductivity profiles afterthe last column with different feed column lengths (first column was1.45 m in test 4a, 3.00 m in test 2a and 1.95 m in test 5a).

FIG. 2 b is a zoomed part of FIG. 2 a to show better the detectedconcentration differences between sucrose and betaine peaks and also thedifference in tailing parts of conductivities.

FIG. 3 shows the conductivities after column 3.

DESCRIPTION OF THE INVENTION

The present invention relates to a sequential SMB equipment having ashallow resin bed compartment as a feed column. Furthermore, the presentinvention relates to a method for fractionating a solution by asequential chromatographic SMB process in which a shallow resin bedcompartment as a feed column is used. A shallow resin bed compartmentused as a feed column improves the performance figures of the sequentialSMB equipment and separation process essentially. The so-called viscousfingering phenomenon is substantially minimized and the tailing effectof the chromatograms is then correspondingly decreased. The tailingeffect of the chromatograms is a real problem with industrialchromatographic applications where the linear flows and loads of drysubstances are heavy. In addition, the shallow resin bed compartmentdesign minimizes resin movement. The resin movement in a column israndom and as being irregular and turbulent, blends the frontiers anddecreases the separation results of an SMB process.

The invention relates to an equipment for fractionating a solution by asequential chromatographic SMB process, comprising a feed column and oneor several other columns connected in series, said feed column and saidother columns including a chromatographic separation resin bed. Theinvention is characterized in that the feed column consists of orcomprises a compartment where the resin bed is shallower than that ofone or more of the other columns of the equipment.

In the following description and the claims, the above-mentionedexpression “a compartment where the resin bed is shallower than that ofone or more of the other columns of the equipment”0 is also referred toas “a shallow resin bed compartment”. In connection with the presentinvention, the shallow resin bed compartment refers to a columncompartment including a resin bed which is shallower than the resin bedof one or more of the other columns of the equipment.

In one embodiment of the invention, the shallow resin bed compartment isthe sole compartment of the feed column. In this embodiment of theinvention, the feed column is composed of one compartment only,including a resin bed which is shallower than that of one or more of theother columns of the equipment. In one embodiment of the invention, theresin bed of the feed column is shallower than that of the next columnof the equipment. The resin bed of the feed column may also be shallowerthan the resin bed of any of the other columns of the equipment. As atypical example, the equipment may consist of a short feed column with ashallow resin bed and one or more other columns with a higher resin bed.In one embodiment of the invention, said one or more other columns havean equal height. In the latter embodiment of the invention, said shallowresin bed compartment of the feed column is shorter than the resin bedof any of the other columns of the equipment.

In another embodiment of the invention, the feed column comprises one,two or several shallow resin bed compartments. In this embodiment of theinvention, the feed column is divided into two or more compartments,which form said shallow resin bed compartments. In a preferredembodiment of the invention, the first of said shallow resin bedcompartments is shorter than the others. As a typical example, the feedcolumn may be divided into two compartments, the resin bed of the firstcompartment being shorter than that of the second compartment. The feedcolumn may also be divided into two compartments with an equal height.It is also possible to divide the feed column into more than twocompartments, whereby the resin bed of the first compartment ispreferably shorter than the resin bed of the others.

In a preferred embodiment of the invention, the feed column comprisesone or two shallow resin bed compartments. In the case of two shallowresin bed compartments, the resin bed of the first shallow resin bedcompartment is preferably shallower than the resin bed of the secondshallow resin bed compartment.

The height of the resin bed of the shallow resin bed compartment istypically equal to or less than 16.7% of the total height of the resinbeds of the columns of the equipment. In a preferred embodiment of theinvention, the height of the shallow resin bed compartment is typicallyequal to or less than 15% of the total height of the resin beds of thecolumns of the equipment. In another preferred embodiment of theinvention, the height of the shallow resin bed compartment is equal toor less than 12.5% of the total height of the resin beds of the columnsof the equipment. In a still more preferred embodiment of the invention,the height of the shallow resin bed compartment is equal to or less than10% of the total height of the resin beds of the columns of theequipment.

The height of the chromatographic separation resin bed of said feedcolumn, said shallow resin bed compartment thereof and said othercolumns preferably corresponds to the height of said column or saidcompartment. However, the height/volume of the resin bed of the columnsof the equipment may even be less than the height/volume of the columns.

An economic way of carrying out the present invention in the SMB systemsalready existing is to divide the existing feed column into two or morecompartments of equal or different height. Accordingly, in thisembodiment of the invention, the equipment of the present invention maycontain two or more shallow resin bed compartments as a feed column. Thefirst compartment of the feed column is preferably shorter than theothers. In practice, the division of the feed column into two or morecompartments may be carried out by installing an extra plate or plateswith a collecting device for the solution to be fractionated. Aperforated plate that permeates the solution to be fractionated may alsobe used.

Chromatographic separation resins are used as a column packing material.The resins are typically ion exchange resins, especially cation or anionexchange resins. The resin is selected depending on the raw materialmixture and/or the products to be recovered. The resins and theirproperties are well known to those skilled in the art.

Said one or several other columns of the equipment typically comprise upto 10 columns, preferably 2 to 5 other columns. In one preferredembodiment of the invention, a combination of a feed column and 2 to 5other columns is used, whereby the feed column and said other columnshave an equal height. The feed column has been divided into twocompartments so that the first compartment of the feed column is shorterthan the second compartment.

In addition to the feed column including at least one shallow resin bedcompartment and one or several other columns connected in series, thechromatographic equipment employed in the present invention typicallycomprises fluid conduits connecting the columns, solution and eluantcontainers, feed and eluant conduits, recycle and feed pumps, heatexchangers, product fraction withdrawal conduits and valves, flow andpressure regulators, and on-line concentration, density, opticalactivity and conductivity meters.

The present invention also relates to a method for fractionating asolution into two or more fractions by a sequential chromatographic SMBprocess with an equipment comprising a feed column and one or severalother columns connected in series, said feed column and said othercolumns including a chromatographic separation resin bed, wherein saidfractions are recovered during a multi-step sequence comprising afeeding phase, an eluting phase and a circulation phase. The method ofthe invention is characterized in that said feeding phase is carried outon a feed column consisting of or comprising a compartment where theresin bed is shallower than that of one or more of the other columns ofthe equipment.

Preferred embodiments of the method of the invention are the same asdescribed above for the equipment of the invention.

The sequential SMB method used in the present invention typicallycomprises three basic phases: a feeding phase, an elution phase and acirculation phase. The method is carried out using an equipmentcomprising a feed column and one or more other columns, which include achromatographic separation resin bed. During the feeding phase, a feedsolution and possibly also an eluant during a simultaneous elutingphase, is introduced into the feed column consisting of or comprising acompartment where the resin bed is shallower than that of one or more ofthe other columns of the equipment, and simultaneously a productfraction or fractions are withdrawn. During the eluting phase, theeluant is introduced into a predetermined column or predeterminedcolumns, and during these phases two, three or even four productfractions are withdrawn. During the circulation phase all columns areconnected into a loop, whereby no feed solution or eluant is supplied tothe columns and no products are withdrawn. However, the circulation assuch takes place during all three phases.

In one embodiment of the invention, the sequential SMB process of theinvention typically comprises the following phases:

a) a feeding phase, wherein the feed solution is fed into the feedcolumn and optionally simultaneously eluant is fed into a subsequentcolumn, and during the feeding phase at least one product fractionand/or one other fraction other than the product is collected from thesame or subsequent column,

b) a circulation phase, wherein all the columns of the equipment areconnected into a loop and nothing is fed into or collected from thesystem,

c) an eluting phase, wherein the eluant is fed into one of the columnsand a residual fraction (a by-product fraction including mainly organicand/or inorganic salts, non-sugars, colour molecules with a highmolecular mass and some oligosaccharides) and optionally a secondproduct fraction or fractions is/are collected from the same or from thesubsequent columns,

phases a) to c) are used during one cycle one to several times.

The present invention is well suitable for separating substances thatare difficult to separate from mixtures containing them. Such mixturesinclude molasses, vinasses, beet-derived juices, starch, wood and/orbagasse hydrolysates, invert sugar mixtures, sulphite cooking liquors,milk whey solutions and other lactose-containing solutions, lactulose-,maltose-, and/or malti-tol-containing solutions, fructose/glucose syrupsand the like. Preferably the solution to be fractionated is a molassesolution, a vinasse solution or a sulphite cooking liquor. The molassesolution preferably comprises beet and/or cane molasses. In the presentinvention sulphite cooking liquor refers to a liquor employed in thecooking of sulphite cellulose or a part thereof, a liquor ensuing fromthe cooking or a part thereof, a liquor used in the sulphite cooking ora part thereof or a liquor removed from the sulphite cooking liquorduring the cooking or a part thereof. In general, the biggest gain ofthe present invention is achieved in separations where the saltconcentration in the feeding phase is high, i.e. in separations wherethe raw material contains salts in considerable amounts, such as beetmolasses, vinasse and sulphite cooking liquor mentioned above. The saltcontent of the raw material may be up to 40% or even up to 65%, based onDS (dry substance content). For instance, the salt content of beetmolasses may be up to 30.5% on DS, that of vinasse up to 61.1% on DS andthat of sulphite cooking liquor up to 37.2% on DS.

The products that are recovered using the equipment and/or method of thepresent invention include sucrose, fructose, glucose, betaine, rhamnose,arabinose, mannose, raffinose, lactose, maltose, maltitol, inositol,mannitol, xylitol, xylose, sorbitol, and amino acids.

In one embodiment of the invention, a molasse solution is fractionatedinto sucrose and betaine.

The eluants employed are well known to those skilled in the art andinclude water, organic solvents such as alcohols, aqueoussalt-containing solutions, or mixtures thereof.

The flow rate may depend on the raw material mixture, the products to berecovered, the resin employed and/or other specific process parameters,such as the number of separation profiles and cycles.

As described above, the equipment and/or method of the present inventionimprove the SMB separation capacity. The improved capacity is achievedby using a shallow resin bed compartment as a feed column.

The present invention will be further clarified by the following examplewhich is intended to be purely exemplary of the invention.

EXAMPLE

The purpose of this study was to show how the length of the feed columnaffects the separation profile in a batch mode SMB process. Further, theoptimum feed column configuration in molasses separation was studied.

In this example, the term “fraction sample”0 refers to a representingsample of a product fraction, taken from the separation process duringthe fractionation of the product fraction. In a molasses separationprocess, such product fractions include sucrose fraction, raffinatefraction and betaine fraction, for example. These fraction samples arethen analyzed in regard to components which are separated into eachfraction.

The term “profile sample”0 refers to one spot sample collected during afew seconds from the separation profile. Several profile samples, forexample 20 to 40 samples are collected per separation profile. Theprofile samples are collected at regular time intervals (for instancewith the intervals of 2 to 4 minutes), until the whole profile haspassed the point where the samples are collected. The profile samplesare then analyzed in the same way as the fraction samples.

Tests were carried out with an SMB-equipment having a column diameter of0.2 m and a total bed length of 18.45 meters. The total length of thefirst two columns was 4.45 m. Separation resin (Lewatit) having a beadsize of 0.37 mm was used as the separation resin. The resin wasbackwashed before the molasses tests. The first two columns were packedwithout NaCl-solution so that there was some room for resin expansionand shrinking. The last five columns were packed with 8% NaCl-solution.

Molasses used was beet molasses. It was pretreated as follows:carbonation with 1.5 -1.8%/DS Na₂CO₃, pH-adjustment with 50% NaOH (pHabout 9.5 -9.7), Seitz-filtration (Kenite 300 as a precoat in an amountof 1 kg/m² and bodyfeed about 0.5%/DS) and the final pH-adjustment withHCl (approx. 0.2 units down). Molasses was finally diluted to a drysubstance content of 55 g/100 g with ion-exchanged water. Table 1 showsthe analyses of feed molasses used in test 1a. TABLE 1 Feed analyses intest 1a Beet molasses after pretreatment Dry substance content 55.4 offeed, g/100 g PH 9.68 Conductivity, 13.3 mS/cm Sucrose, %/DS 59.2Betaine, %/DS 6.8 Others, % DS 34.0

The lengths of the two first columns were varied to have differentlengths in them. Altogether three different feed column configurationswere tested. Table 2 shows the column configurations used in thedifferent tests. The flow rate in every test was kept constant (100l/h). TABLE 2 Feed column configurations in different tests Col. Col.Test 1 2 Col. 3 Col. 4 Col. 5 Col. 6 Col. 7 numbers (m) (m) (m) (m) (m)(m) (m) 1a + 1b + 1.45 3.00 3.00 2.50 3.00 2.50 3.00 1c + 1d 4a + 4b1.45 3.00 2a + 2b + 3.00 1.45 2c + 2d 3a + 3b + 3.00 1.45 3c + 3d 5a +5b + 1.95 2.50 5c + 5d 6a + 6b 1.95 2.50a/b = fraction samples/on-line data from two following feeds,c = profile samples from column 2,d = profile samples from column 7

The resin was balanced with several feed pulses before testing. Testswere carried out so that the first fraction samples (e.g. 1a) werecollected from the third out coming feed and the second samples (e.g.1b) from the fourth feed when the fifth feed was still going in to thefeed column (to have a best possible situation without any disturbancedue to resin movings etc. and also to simulate the situation in theresin bed when a 2-profile SMB-sequence would have run). Every columnconfiguration was tested twice to minimize possible errors caused byprocess instruments like flow meters etc. From tests 6a and 6b nofraction samples were collected. The profile samples from partialcolumns 2 and 7 were collected next day (e.g. 1c/1d). The process data(on-line instruments like conductivity from partial columns 1/2, 3, 5and 7, concentration from column 7) were collected from every test. Theon-line data seemed to give the best information of separation behaviourand that is why some fraction samples and profile samples were notcollected from the latest tests.

A total of three different feed column configurations were tested asseen in table 2. In the first configuration the height of the feedcolumn was 1.45 m, in the second configuration it was 3.00 m and in thethird configuration 1.95 m. All the tests were carried out with the samesequence program to have exactly the same fraction limits to get an ideahow different compounds are divided in different fractions. The on-lineprofiles of tests 2 (“long”), 4 (“short”) and 5 (“mid”) from the lastcolumn are also presented in FIGS. 2 a and 2 b.

As seen in FIG. 1 the sucrose content in the betaine fraction isincreasing (the sucrose peak is tailing more) when the feed column islonger. The difference in the residual fractions is much smaller.

As seen in FIGS. 2 a, 2 b and 3 the conductivity profile is tailing morewhen the first column is longer and also the conductivity peak issmoother. The separation between sucrose and betaine is better with ashorter feed column as seen in FIG. 2 b. The difference between the1.45m and 1.95 m columns is small, but according to FIGS. 1 and 2 bbetaine is separating slightly better when the height of the firstcolumn is 1.45 m.

These results show that a short feed column (or a feed column dividedinto two compartments instead of one longer column) gives benefit forseparation performance.

It will be obvious to a person skilled in the art that, as thetechnology advances, the inventive concept can be implemented in variousways. The invention and its embodiments are not limited to the examplesdescribed above but may vary within the scope of the claims.

1-30. (canceled)
 31. A method for fractionating a solution into two ormore fractions by a sequential chromatographic SMB process withequipment comprising a feed column and one or several other columnsconnected in series, said feed column and said other columns including achromatographic separation resin bed, wherein said fractions arerecovered during a multi-step sequence comprising a feeding phase, aneluting phase and a circulation phase, characterized in that there isachieved a decreased tailing effect of the separation profile in thefractionation by carrying out said feeding phase on a feed columnconsisting of or comprising a compartment where the resin bed isshallower than that of one or more of the other columns of theequipment.
 32. A method according to claim 31, characterized in thatsaid shallow resin bed compartment is the sole compartment of the feedcolumn.
 33. A method according to claim 31, characterized in that thefeed column comprises selectively one, two or several of said shallowresin bed compartments.
 34. A method according to claim 33,characterized in that the resin bed of the first of said shallow resinbed compartments is shallower than the resin beds of the remainingcompartments.
 35. A method according to claim 31, characterized in thatthe resin bed of said shallow resin bed compartment of the feed columnis shallower than that of a next column of the equipment.
 36. A methodaccording to claim 31, characterized in that the resin bed of saidshallow resin bed compartment of the feed column is shallower than thatof any of the other columns of the equipment.
 37. A method according toclaim 33, characterized in that the feed column comprises selectivelyone or two shallow resin bed compartments.
 38. A method according toclaim 37, characterized in that the resin bed of the first shallow resinbed compartment is shallower than that of the second shallow resin bedcompartment.
 39. A method according to claim 31, characterized in thatsaid shallow resin bed compartment is arranged by dividing the feedcolumn into first and second compartments, where the resin bed of thefirst compartment is shallower than the resin bed of the secondcompartment.
 40. A method according to claim 31, characterized in thatsaid shallow resin bed compartment is arranged by dividing the feedcolumn into first, second and third compartments, where the resin bed ofthe first compartment is shallower than the resin bed of the second andthird compartment.
 41. A method according to claim 31, characterized inthat said shallow resin bed compartment is formed by dividing the feedcolumn into two compartments with equal height.
 42. A method accordingto claim 31, characterized in that said shallow resin bed compartment isformed by dividing the feed column into three compartments with eachbeing of equal height.
 43. A method according to claims 31,characterized in that the height of the resin bed of said shallow resinbed compartment is equal to or less than 16.7% of the total height ofthe resin beds of the columns of the equipment.
 44. A method accordingto claim 31, characterized in that the height of the resin bed of saidshallow resin bed compartment is equal to or less than 15% of the totalheight of the resin beds of the columns of the equipment.
 45. A methodaccording to claim 31, characterized in that the height of the resin bedof said shallow resin bed compartment is equal to or less than 12.5% ofthe total height of the resin beds of the columns of the equipment. 46.A method according to claim 31, characterized in that the height of theresin bed of said shallow resin bed compartment is equal to or less than10% of the total height of the resin beds of the columns of theequipment.
 47. A method according to claim 31, characterized in that theheight of the chromatographic separation resin bed of said feed column,said shallow resin bed compartment thereof and said other columnscorresponds to the height of said column or of said compartment.
 48. Amethod according to claim 31, characterized in that said solution whichis fractionated is selected from the group of materials consisting of amolasses solution, a vinasse solution and a sulphite cooking liquor. 49.A method according to claim 48, characterized in that said solutionwhich is fractionated is a molasses solution.
 50. A method according toclaim 49, characterized in that there are recovered a fraction which isenriched in betaine and a fraction which is enriched in sucrose.
 51. Amethod according to claim 31, characterized in that said solution whichis fractionated is a solution containing high amounts of salts.